Candida albicans is the most important of the opportunistic fungal pathogens in terms of morbidity and mortality among immunocompromised individuals. Although many studies have been done on this organism and the disease it causes, many questions remain concerning host C. albicans interactions. The fungus is capable of undergoing a yeast to hyphal form transformation upon the invasion of host tissue. In fact, this morphogenic shift is thought to relate to the pathogenetic potential of the organism. Control and regulation of C. albicans morphogenesis is not understood, and genetic elements involved have not been identified. The long range goal of this research is to isolate genes and regulatory DNA sequences directly involved in a yeast to hyphal transformation. Completion of the specific aims of this proposal will provide the groundwork for realization of the long range goal. DNA repeat elements will be cloned and characterized with regard to specificity for C. albicans DNA. The cloned repeat elements will be used as probes to determine if they or flanking DNA regions become methylated during morphogenesis. Finally, mRNA (cDNA) cloning techniques will be developed to allow identification of expression of mRNA species unique to initiation of a yeast to hyphal form transition. MBRS students will be trained in all phases of the studies and will develop the ability to evaluate data, critically review literature reports, design experiments, present their findings at scientific meetings, and write research manuscripts.